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Amyotrophic lateral sclerosis & frontotemporal degeneration
Published

Cerebrospinal fluid levels of NfM in relation to NfL and pNfH as prognostic markers in amyotrophic lateral sclerosis

Authors

Jennie Olofsson, Sofia Bergström, Sára Mravinacová, Ulf Kläppe, Linn Öijerstedt, Henrik Zetterberg, Kaj Blennow, Caroline Ingre, Peter Nilsson, Anna Månberg

Abstract

Amyotroph Lateral Scler Frontotemporal Degener. 2024 Nov 22:1-11. doi: 10.1080/21678421.2024.2428930. Online ahead of print.

ABSTRACT

Objective: To evaluate the prognostic potential of neurofilament medium chain (NfM) in CSF from patients with ALS and explore its relationship with the extensively studied neurofilament light chain (NfL) and phosphorylated heavy chain (pNfH). Method: CSF levels of NfL, NfM, and pNfH were analyzed in 235 samples from patients with ALS, ALS mimics, and healthy controls in a well-characterized cohort from Karolinska ALS Clinical Research Center in Stockholm, Sweden. NfM levels were analyzed using an antibody-based suspension bead-array and NfL and pNfH levels were measured using ELISA. Clinical data, including ALS Revised Functional Rating Scale (ALSFRS-R), and survival outcomes were utilized for disease progression estimations. Result: Increased NfM levels were observed in patients with ALS compared with mimics and healthy controls. Similarly, higher NfM levels were found in fast compared with slow progressing patients for baseline and longitudinal progression when evaluating both total and subscores of ALSFRS-R. These findings were consistent with the results observed for NfL and pNfH. All three proteins, used individually as well as in combination, showed comparable performance when classifying fast vs slow progressing patients (AUCs 0.78-0.85). For all neurofilaments, higher survival probability was observed for patients with low CSF levels. Conclusion: Based on this cross-sectional study, the prognostic value provided by NfM aligns with the more established markers, NfL and pNfH. Additional investigations with independent cohorts and longitudinal studies are needed to further assess the potential added value of NfM.

PMID:39575564 | DOI:10.1080/21678421.2024.2428930

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg